Respiratory viral infections represent a major risk factor for the development of asthma. Moreover, severe influenza injury can result in ineffective repair and persistent loss of pulmonary function. The enduring changes caused by viral-induced lung injury that might explain chronic disease are not understood. We recently identified ectopic tuft / solitary chemosensory cells (SCCs) arising in the distal lung after H1N1 influenza infection. Since SCCs are increasingly recognized as critical orchestrators of both inflammation and epithelial tissue regeneration and remodeling, we posit that they are a likely driver of chronic lung pathology. This proposal will address the central hypothesis that inactivation / ablation of ectopic SCCs will promote the resolution of dysplastic remodeling and reduce chronic Th2-biased inflammatory disease, but may also increase susceptibility to pathogens controlled by Th2 responses following influenza infection. The major aims to address this hypothesis are to 1) ascertain the effects of SCC presence and specific SCC-derived signals on epithelial progenitor cells (fate and proliferation) during repair, and 2) determine whether the development of SCCs impacts Th2-mediated inflammatory disease (asthma) or parasitic protection. Completion of this project will validate SCCs as important drivers of pulmonary disease and will also facilitate identification of specific SCC effector pathways that could allow for preservation of host-protective benefits while attenuating their contribution to pathology.